New research looking at the key reasons for poor vision in wet AMD patients following treatment found almost one in 10 eyes showed visual acuity that corresponded with legal blindness at two years after the onset of anti-VEGF therapy. The study, published in Ophthalmology, also reported central macular atrophy was the source of poor vision 60% of the time, while central subretinal fibrosis was responsible for the other 40%.

“Clearly, atrophy and fibrosis represent the most important barriers to good visual outcomes in neovascular AMD,” says researcher Tiarnan Keenan, MD, PhD, of the National Eye Institute. “Both are essentially irreversible, though subretinal fibrosis may be preventable in many cases.”

The study enrolled AREDS2 participants who underwent refracted BCVA testing, an ophthalmoscopic exam and fundus photography both at baseline and during annual visits.

Of the 594 eligible eyes, about 9% had a BCVA of 20/200 or worse at two years. The approximate BCVA was roughly 15 letters (20/500) vs. about 70 letters (20/40) in the other group. Of the 55 eyes who had fundus photography at two years, 60% had central macular atrophy and 40% had central subretinal fibrosis, which the researchers determined as the principal cause for poor vision.

The group with poor BCVA had a higher number of non-white participants (about 9% vs. 2%), lower BCVA earlier than the two-year mark at 38 letters (Snellen equivalent, 20/160) vs. about 72 letters (Snellen equivalent, 20/40). This group also encompassed more individuals who developed macular atrophy earlier than the study’s endpoint (about 27% vs. 12%) and who had macular hemorrhage (roughly 26% vs. 13%) and fewer anti-VEGF injections (approximately eight vs. 10).

Early diagnosis of neovascular disease and avoiding under-treatment with anti-VEGF therapy may help prevent subretinal fibrosis, Dr. Keenan explains. Since type 2 lesions with subretinal hyperreflective material have a high risk of fibrosis, these eyes require more intensive treatment and closer monitoring, he adds. Despite the failure of three recent Phase III trials of combined anti-VEGF and anti-PDGF therapy, adjunctive therapies to target fibrosis remain an area of active research, he adds.

For macular atrophy, cases caused by poorly controlled exudation also require earlier diagnosis of neovascular disease and more aggressive anti-VEGF therapy, Dr. Keenan says. However, other cases are likely caused by natural progression to geographic atrophy, independent of neovascularization. For these eyes, as for eyes with pure geographic atrophy, approaches to decrease the risk of atrophy and slow its progression may be on the horizon, he suggests.

“Overall, early diagnosis of neovascular AMD and adequate treatment with anti-VEGF therapy are vital,” Dr. Keenan says. “In the future, this may be aided by approaches such as home OCT monitoring, longer-acting anti-VEGF drugs and drug delivery systems.”

Okeagu CU, Agrón E, Vitale S, et al. Principal cause of poor visual acuity after neovascular age-related macular degeneration: age-related eye disease study 2 report number 23. Ophthalmology. 2021;5(1):23-31.